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NICE has yesterday published final draft guidance recommending 2 new treatment options for some people who have conditions that put them at extremely high risk of heart attacks or strokes.

The draft guidance recommends alirocumab (Praluent, Sanofi) and evolocumab (Repatha, Amgen) for adults with primary hypercholesterolaemia or mixed dyslipidaemia to help reduce their risk of cardiovascular disease.

The drugs are recommended for people with these conditions whose cholesterol levels are not controlled adequately using other drugs such as statins, or who can’t tolerate statins because of their side effects or have another condition which means they can’t take them.

People with primary hypercholesterolaemia or mixed dyslipidaemia have an increased risk of cardiovascular disease because long term raised cholesterol levels accelerate the build-up of fatty deposits in the arteries (atherosclerosis). The narrowing of the arteries can eventually lead to cardiovascular disease such as angina, heart attacks and strokes.

People with the inherited form of the disease (familial hypercholesterolaemia) have raised cholesterol levels from birth, so their risk of cardiovascular disease increases from an early age to as high as 50% in men by the age of 50 years and at least 30% in women by the age of 60 years.

The draft guidance recommends the drugs, which are not licensed for everyone who has high cholesterol levels, only if they are provided at the discounted price agreed with the companies.

The committees heard that alirocumab reduced levels of LDL-cholesterol (so-called ‘bad cholesterol’) by up to 62% compared with placebo, and up to 40% compared with ezetimibe, another commonly used drug to lower cholesterol. Similar reductions were seen with evolocumab.

Both alirocumab and evolocumab are given by self-administered injection once every 2 weeks (once a month for the 420 mg dose of evolocumab).

Unlike statins, which work by slowing down the production of cholesterol by the liver, alirocumab and evolocumab work by blocking a protein called PCSK9, allowing the liver to remove cholesterol from the blood.

Cardiovascular disease was the cause of approximately 150,000 deaths in England in 2012.

Professor Carole Longson MBE, Director of the NICE Centre for Health Technology Evaluation, said: “We are very pleased to be able to recommend alirocumab and evolocumab. People with hypercholesterolaemia or mixed dyslipidaemia who have a high risk of a heart attack or stroke despite taking the highest tolerated dose of other cholesterol-lowering drugs, have very few treatment options.

“The committee concluded that both drugs are effective in reducing levels of ‘bad cholesterol’ when compared with placebo, ezetimibe or statins in people with hypercholesterolaemia or mixed dyslipidaemia.

“However, both drugs are relatively expensive, costing over £4000 per patient per year compared with about £350 for ezetemibe. Therefore the draft guidance recommends alirocumab and evolocumab as a cost effective use of NHS resources only with the discounts agreed with the companies and only for people with hypercholesterolaemia or mixed dyslipidaemia whose cholesterol is still not under control despite making changes to their lifestyle and taking other cholesterol-lowering drugs.”

Until final guidance is issued, NHS bodies should make decisions locally on the funding of specific treatments. Once NICE issues its final guidance on a technology, it replaces local recommendations across the country.

For more information call the NICE press office on 0300 323 0142/pressoffice@nice.org.uk or out of hours on 07775 583 813.

Notes to Editors

About the draft guidance for alirocumab

1. The draft guidance will be available on the NICE website athttp://www.nice.org.uk/guidance/indevelopment/gid-tag512 from 6 May. Embargoed copies of the FAD are available via https://share.nice.org.uk. To access the shared folder, the username is PressMedia1 – the password will be sent out in a separate email. If you have not received the password, please contact the NICE press office.
2. The draft guidance states:

          Alirocumab is recommended as an option for treating primary hypercholesterolaemia or mixed dyslipidaemia, only if:

• Low-density lipoprotein concentrations are persistently above the thresholds specified in table 1 despite maximal tolerated lipid-lowering therapy. That is, either the maximum dose has been reached, or further titration is limited by intolerance (as defined in NICE’s guideline on familial hypercholesterolaemia: identification and management).
• The company provides alirocumab with the discount agreed in the patient access scheme.

Table 1 Low-density lipoprotein cholesterol concentrations above which alirocumab / evolocumab is recommended

1. Alirocumab is an antibody that targets a protein called PCSK9. PCSK9 reduces the number of receptors on the liver that remove LDL cholesterol (also known as ‘bad’ cholesterol) from the blood. By blocking PCSK9’s ability to work, more receptors are available to get rid of LDL cholesterol from the blood and, as a result, lower LDL cholesterol levels.
2. Alirocumab has a marketing authorisation in the UK for treating ‘adults with primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia, as an adjunct to diet:

• in combination with a statin or statin with other lipid lowering therapies in patients unable to reach LDL-C goals with the maximum tolerated dose of a statin or,
• alone or in combination with other lipid-lowering therapies in patients who are statin-intolerant, or for whom a statin is contraindicated.

Alirocumab is given by subcutaneous injection. The recommended dose is either 75 mg or 150 mg every 2 weeks.

1. Alirocumab costs £168 for a 75 mg or 150 mg single-use prefilled pen (excluding VAT, company’s submission).  The annual cost of treatment per patient is £4,383 for 75 mg or 150 mg every 2 weeks.
2. The company has agreed a patient access scheme with the Department of Health that will provide a simple discount to the list price of alirocumab with the discount applied at the point of purchase or invoice. The level of the discount is commercial in confidence.
3. The most likely cost-effectiveness estimates (given as an ICER) for alirocumab are:

• For the non-familial hypercholesterolaemia high-risk cardiovascular disease (secondary prevention) population:
  • between £24,800 and £44,300 per QALY gained for alirocumab and a statin plus ezetimibe compared with a statin and ezetimibe
  • the ICER would be below £30,000 per QALY gained at an LDL‑C level of 4.1 mmol/litre.
• For the non-familial hypercholesterolaemia recurrent events/polyvascular disease (secondary prevention) population:
  • between £19,300 and £34,000 per QALY gained for alirocumab and a statin plus ezetimibe compared with a statin and ezetimibe
  • the ICER would be below £30,000 per QALY gained at an LDL‑C level of 3.5 mmol/litre.
• For the heterozygous-familial hypercholesterolaemia (primary prevention) population:
  • between £37,000 and £50,000 per QALY gained. considered for alirocumab and a statin plus ezetimibe compared with a statin and ezetimibe
  • the ICER would be below £30,000 per QALY gained at an LDL‑C level of 6.1 mmol/litre.
• For the heterozygous-familial hypercholesterolaemia (secondary prevention) population:
  • between £20,000 and £24,000 per QALY gained for alirocumab and a statin plus ezetimibe compared with a statin and ezetimibe
  • the ICER would be below £30,000 per QALY gained at an LDL‑C level of 4.0 mmol/litre.

 About the draft guidance for evolocumab

1. The draft guidance will be available on the NICE website athttp://www.nice.org.uk/guidance/indevelopment/gid-tag498 from 6 May.
2. 2. The draft guidance states:

Evolocumab is recommended as an option for treating primary hypercholesterolaemia or mixed dyslipidaemia , only if:

• the dosage is 140 mg every 2 weeks
• LDL-C concentrations are persistently above the thresholds specified in table 1 (above) despite maximal tolerated lipid-lowering therapy. That is, either the maximum dose has been reached or further titration is limited by intolerance (as defined in section 1.3.1.11 of NICE’s guideline on familial hypercholesterolaemia: identification and management), and
• the company provides evolocumab with the discount agreed in the patient access scheme.

1. Evolocumab is an antibody that targets a protein called PCSK9. PCSK9 reduces the number of receptors on the liver that remove LDL cholesterol (also known as ‘bad’ cholesterol) from the blood. By blocking PCSK9’s ability to work, more receptors are available to get rid of LDL cholesterol from the blood and, as a result, lower LDL cholesterol levels.
2. Evolocumab has a marketing authorisation in the UK for treating adults with primary hypercholesterolaemia (heterozygous-familial and non-familial) or mixed dyslipidaemia, as an adjunct to diet:

• in combination with a statin, or a statin plus other lipid-lowering therapies in patients unable to reach LDL‑C goals with the maximum tolerated dose of a statin or,
• alone or in combination with other lipid-lowering therapies in patients who cannot tolerate or cannot be given statins.

Evolocumab is given by subcutaneous injection. The recommended dose in the summary of product characteristics is either 140 mg every 2 weeks or 420 mg once monthly.

1. Evolocumab costs £170.10 for a 140‑mg prefilled pen or syringe (excluding VAT; MIMS, March–May 2016). The annual cost of treatment per patient is about £4448.60 for 140 mg every 2 weeks.
2. The company has agreed a patient access scheme with the Department of Health. This scheme provides a simple discount to the list price of evolocumab, with the discount applied at the point of purchase or invoice. The level of the discount is commercial in confidence.
3. The most likely cost-effectiveness estimates (given as an ICER) for evolocumab are:

• For non-familial hypercholesterolaemia with progressive, symptomatic CVD, and persistently high LDL‑C concentrations above 4.0 mmol/litre, the company’s ICERs were lower than £37,700 (based on the LAPLACE‑2 population) and £29,200 (based on the Clinical Practice Research Datalink population) per QALY gained.
• For heterozygous-familial hypercholesterolaemia with CVD, and persistently high LDL‑C concentrations above 3.5 mmol/litre, the company’s ICER was lower than £33,600.
• For heterozygous-familial hypercholesterolaemia without CVD with persistently high LDL-C concentrations above 5.0 mmol/litre, the company’s ICER was lower than £18,400 per QALY gained.

 About primary hypercholesterolaemia

1. In primary non-familial hypercholesterolaemia, a number of genes interact with dietary and other lifestyle factors such as smoking and lack of exercise to cause high cholesterol levels. Primary non-familial hypercholesterolaemia affects an estimated 1.5 million people in England.
2. Primary heterozygous-familial hypercholesterolaemia is an inherited condition caused by a faulty gene and affects about 106,000 people in England. People with this condition have raised cholesterol levels from birth.

About mixed dyslipidaemia

• Mixed dyslipidaemia is defined as elevations in LDL cholesterol and triglyceride levels that are often accompanied by low levels of high-density lipoprotein (HDL) cholesterol. Treatment for mixed dyslipidaemia is partly determined by the LDL-C concentration.

About NICE

The National Institute for Health and Care Excellence (NICE) is the independent body responsible for driving improvement and excellence in the health and social care system. We develop guidance, standards and information on high-quality health and social care. We also advise on ways to promote healthy living and prevent ill health.

Our aim is to help practitioners deliver the best possible care and give people the most effective treatments, which are based on the most up-to-date evidence and provide value for money, in order to reduce inequalities and variation.

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